The present invention describes, inter alia, oxygen delivery agents or blood substitutes comprising a fluorinated gas and a stabilizing material, methods of using the oxygen delivery agents or blood substitutes, and apparatus for making and delivering the oxygen delivery agents or blood substitutes.
A theoretical assessment of oxygen delivery agents and the efficacy of loading and unloading oxygen is described from the standpoint of the partial pressures of oxygen in the lungs, blood, and tissues by Van Liew, et al., J. Appl. Physiol., 81(1):500-508 (1996), and Burkard et al, J. Appl. Physiol., 77(6):2874-2878 (1994). Liquid perfluorocarbons, such as perfluorooctylbromide, perfluorodecalin, perfluorotripropylamine and perfluorotributylamine, have been investigated as oxygen-transporting blood substitutes by, for example, Lowe, Comp. Biochem. Physiol., 87A:825-838 (1987). However, these liquid perfluorocarbons boil at temperatures far above physiological conditions, and thus have a limited ability to thermally expand. This limitation imposes a practical constraint on the amount of infused liquid perfluorocarbon that may be administered to a patient in need of an oxygen-carrying blood substitute. Toxicity problems associated with liquid perfluorocarbon emulsions have also imposed significant limitations on their use, as described, for example, by Jing and Cooper, Biomat. Art. Cells Art. Org., 18:107-117 (1990).
There is a need for oxygen delivery agents or blood substitutes that overcome the problems associated with the prior art. The present invention is directed to these, as well as other, important ends.
The present invention describes a method for oxygen delivery comprising administering to a patient a composition, in an aqueous carrier, comprising a fluorinated gas and a stabilizing material. The composition may further comprise oxygen before it is administered to the patient, or it may be administered without oxygen, whereby oxygen is added to the composition by the patient""s own respiratory processes upon circulation through the patient""s lungs. The method may also comprise imaging the patient with diagnostic ultrasound to monitor the location of the composition and applying therapeutic ultrasound to the patient to facilitate delivery of the oxygen in a desired region of the patient. The stabilizing material may be in a vesicular or non-vesicular form, as desired.
In another embodiment, the present invention describes an oxygen delivery vehicle or blood substitute comprising a composition which comprises a fluorinated gas and a stabilizing material. The composition further comprises oxygen. Preferably, the composition further comprises an aqueous carrier. The stabilizing material may be in a vesicular or non-vesicular form, as desired.
In another embodiment, the present invention describes an apparatus for making an oxygen delivery agent. The apparatus comprises (i) a first vessel containing a stabilizing material, (ii) a second vessel containing a fluorinated compound, (iii) means for mixing the stabilizing material and the fluorinated compound so as to form an oxygen delivery agent. In a preferred embodiment, the apparatus also includes a supply of oxygen and means for introducing oxygen from the supply into the mixture so as to form an oxygen carrying oxygen delivery agent. Preferably, at least one of the vessels is formed by the barrel of a syringe. In one embodiment, the mixing means comprises (i) a device for inducing turbulence into the mixture of stabilizing material and fluorinated compound and (ii) a device for agitating the mixture. The apparatus may further comprise a device for evacuating the contents of the vessels. In one embodiment, the evacuation device comprises a programmable mechanical injector. In another embodiment, the evacuation device comprises a disposable pressurized gas cylinder.
These and other aspects of the invention will become more apparent from the following detailed description.